CN104323986A - Phloroglucinol injection and preparation method thereof - Google Patents
Phloroglucinol injection and preparation method thereof Download PDFInfo
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- CN104323986A CN104323986A CN201310308262.XA CN201310308262A CN104323986A CN 104323986 A CN104323986 A CN 104323986A CN 201310308262 A CN201310308262 A CN 201310308262A CN 104323986 A CN104323986 A CN 104323986A
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- phloroglucinol
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Abstract
The invention belongs to the field of medicine preparations, and provides a phloroglucinol injection. The phloroglucinol injection is composed of an active composition phloroglucinol, an anti-oxidant sodium metabisulfite, propylene glycol, a pH conditioning agent selected from citric acid and sodium citrate, and injection water. The invention also provides a preparation method of the above injection. The prepared phloroglucinol injection solves the problems that a phloroglucinol injection in a conventional dosage form is easy to degrade and bad in stability, and has usage inconvenience because the crystal is easy to precipitate after the phloroglucinol injection is stored at a low temperature for a long time.
Description
Technical field
The invention belongs to field of pharmaceutical preparations, be specifically related to a kind of phloroglucinol injection and preparation method thereof.
Background technology
Phloroglucinol has another name called phlorhizin phenol, phloroglucinol, and chemical name is phloroglucinol.Be widely used in treating acute painful muscle spasms, acute spastic urethra, bladder, renal colic etc. that the disease that caused by smooth muscle spasm causes as digestive system and biliary tract function of patients obstacle clinically.Phloroglucinol belongs to close muscular, non-atropine, the pure flat sliding flesh spasmolytic of non-Semen Papaveris bases, can directly act on the smooth muscle of gastrointestinal tract and urogenital tract.Compared with other smooth muscle spasmolysis medicines, phloroglucinol does not have cholinolytic effect, can not produce the side effect of a series of cholinolytic sample as increased heart rate, arrhythmia etc. while releasing smooth muscle spasm.Animal pharmacological test shows, phloroglucinol only acts on spasm smooth muscle, minimum on normal smooth muscle impact.
China is in the phloroglucinol injection (commodity are called Phloroglucinol) in calendar year 2001 and the large pharmaceutical factory of approved imported France Lafon, and within 2010, domestic phloroglucinol injection also goes on the market.But there is certain defect in above-mentioned injection, cause as contained three phenolic hydroxyl groups due to phloroglucinol its easily oxidized, to photaesthesia and due in water poor solubility and cause its prolonged cold (less than 10 DEG C) to be deposited can crystallization.
Therefore, it is very urgent for developing a kind of new prescription to solve above-mentioned injection Problems existing.
Summary of the invention
The object of the invention is to easily degrades for phloroglucinol injection generates impurity and prolonged cold (less than 10 DEG C) and deposits easy crystallization and cause using the problems such as inconvenient, provides a kind of new phloroglucinol injection and preparation method thereof.
Phloroglucinol injection provided by the invention, be made up of active component phloroglucinol, antioxidant sodium pyrosulfite, propylene glycol, the pH adjusting agent being selected from citric acid and sodium citrate and water for injection, wherein the weight ratio of phloroglucinol, sodium pyrosulfite, propylene glycol, citric acid, sodium citrate, water for injection is: 40:0.05 ~ 0.20:200 ~ 250:6 ~ 10:5 ~ 8:3750 ~ 3800.
Described phloroglucinol injection, its active component can be phloroglucinol anhydride, also can be the hydrate forms of phloroglucinol, as phloroglucinol dihydrate.
Described phloroglucinol injection, wherein the preferred weight ratio of phloroglucinol, sodium pyrosulfite, propylene glycol, citric acid, sodium citrate, water for injection is: 40:0.05:200:6:8:3800.
Described phloroglucinol injection, wherein the preferred weight ratio of phloroglucinol, sodium pyrosulfite, propylene glycol, citric acid, sodium citrate, water for injection is: 40:0.20:225:10:5:3775.
Described phloroglucinol injection, wherein the preferred weight ratio of phloroglucinol, sodium pyrosulfite, propylene glycol, citric acid, sodium citrate, water for injection is: 40:0.1:250:8:6.5:3750.
The present invention provides a kind of preparation method of above-mentioned phloroglucinol injection in addition, it comprises the following steps: (1) takes the sodium pyrosulfite of recipe quantity, propylene glycol, citric acid, sodium citrate are dissolved in recipe quantity water for injection, add recipe quantity phloroglucinol to dissolve, (2) active carbon stirring and adsorbing is added, (3) fill after filtering, sealing by fusing are in ampoule bottle, sterilizing, to obtain final product.
The present invention also provides a kind of preparation method of above-mentioned phloroglucinol injection in addition, it is characterized in that carrying out nitrogen protection operation in dissolving, stirring, fill step, avoids active component phloroglucinol to contact with oxygen.
It is prepared by following steps specifically: (1) takes the sodium pyrosulfite of recipe quantity, propylene glycol, citric acid, sodium citrate are dissolved in recipe quantity water for injection; add recipe quantity phloroglucinol under nitrogen protection to dissolve; (2) add active carbon, under nitrogen protection stirring and adsorbing, (3) filter; nitrogen is passed in ampoule bottle; liquid drug, passes into nitrogen again, sealing by fusing; sterilizing, to obtain final product.
Described active carbon is preferably powdery pharmaceutical charcoal, and its consumption is 0.01% ~ 0.1%(mass volume ratio), preferably 0.1%; The stirring and adsorbing time is 10 ~ 20min, preferred 15min.
Filtration in step (3) comprises the microporous filter membrane or titanium filter stick or polysulfone filter filtration decarburization of first selecting 0.45 ~ 1 μm, then selects microporous filter membrane or the polysulfone filter aseptic filtration of 0.22 μm.
Sterilizing methods in step (3) is final sterilization method, and sterilising conditions is 121 DEG C of moist heat sterilization 8 ~ 30min, preferably 121 DEG C of moist heat sterilization 10 ~ 20min, further preferred 121 DEG C of moist heat sterilization 15min.
Beneficial effect of the present invention: phloroglucinol injection provided by the invention solves phloroglucinol injection in prior art and easily degrades and generate impurity, deposit the problem of easy crystallization because of prolonged cold (less than 10 DEG C); Adopt terminally sterilised sterilization process simultaneously, ensure that the sterility assurance level of injection.
Specific embodiment
Following embodiment is specific preferred embodiment in order to demonstrate the invention, the protection domain be not meant to limit the present invention.
The raw material used in reference example and enforcement 1-4 is produces gained by art methods at same batch.
Reference example 1 is without antioxidant
Preparation technology
Take the adjuvant propylene glycol of recipe quantity, sodium citrate, citric acid to be successively dissolved in recipe quantity water for injection, add recipe quantity phloroglucinol dihydrate and dissolve; Add 0.1%(mass volume ratio) powdery pharmaceutical active carbon, stirring and adsorbing 15min; First use 0.45 μm of filtering with microporous membrane decarburization, then use 0.22 μm of microporous filter membrane aseptic filtration; Get portion filtrate and carry out intermediates content inspection; Fill, sealing by fusing are in ampoule bottle, and 121 DEG C × 15min sterilizing, to obtain final product.
Reference example 2 antioxidant is sodium sulfite
Preparation technology
Take the adjuvant sodium sulfite of recipe quantity, propylene glycol, sodium citrate, citric acid to be successively dissolved in recipe quantity water for injection, add recipe quantity phloroglucinol dihydrate and dissolve; Add 0.1%(mass volume ratio) powdery pharmaceutical active carbon, stirring and adsorbing 15min; First use 0.45 μm of filtering with microporous membrane decarburization, then use 0.22 μm of microporous filter membrane aseptic filtration; Get portion filtrate and carry out intermediates content inspection; Fill, sealing by fusing are in ampoule bottle, and 121 DEG C × 15min sterilizing, to obtain final product.
Reference example 3 is without propylene glycol
Preparation technology
Take the adjuvant sodium pyrosulfite of recipe quantity, sodium citrate, citric acid to be successively dissolved in recipe quantity water for injection, add recipe quantity phloroglucinol dihydrate and dissolve; Add 0.1%(mass volume ratio) powdery pharmaceutical active carbon, stirring and adsorbing 15min; First use 0.45 μm of filtering with microporous membrane decarburization, then use 0.22 μm of microporous filter membrane aseptic filtration; Get portion filtrate and carry out intermediates content inspection; Fill, sealing by fusing are in ampoule bottle, and 121 DEG C × 15min sterilizing, to obtain final product.
Reference example 4pH regulator is different
Take the adjuvant sodium pyrosulfite of recipe quantity, propylene glycol is successively dissolved in recipe quantity water for injection, add recipe quantity phloroglucinol dihydrate and dissolve; Add 1mol/L salt acid for adjusting pH to 4.5; Add 0.1%(mass volume ratio) powdery pharmaceutical active carbon, stirring and adsorbing 15min; First use 0.45 μm of filtering with microporous membrane decarburization, then use 0.22 μm of microporous filter membrane aseptic filtration; Get portion filtrate and carry out intermediates content inspection; Fill, sealing by fusing are in ampoule bottle, and 121 DEG C × 15min sterilizing, to obtain final product.
Embodiment 1
Preparation technology
Take the adjuvant sodium pyrosulfite of recipe quantity, propylene glycol, sodium citrate, citric acid to be successively dissolved in recipe quantity water for injection, add recipe quantity phloroglucinol dihydrate and dissolve; Add 0.1%(mass volume ratio) powdery pharmaceutical active carbon, stirring and adsorbing 15min; First use 0.45 μm of filtering with microporous membrane decarburization, then use 0.22 μm of microporous filter membrane aseptic filtration; Get portion filtrate and carry out intermediates content inspection; Fill, sealing by fusing are in ampoule bottle, and 121 DEG C × 15min sterilizing, to obtain final product.
Embodiment 2
Preparation technology
Take the adjuvant sodium pyrosulfite of recipe quantity, propylene glycol, sodium citrate, citric acid to be successively dissolved in recipe quantity water for injection, add recipe quantity phloroglucinol dihydrate and dissolve; Add 0.1%(mass volume ratio) powdery pharmaceutical active carbon, stirring and adsorbing 15min; First use 0.45 μm of filtering with microporous membrane decarburization, then use 0.22 μm of microporous filter membrane aseptic filtration; Get portion filtrate and carry out intermediates content inspection; Fill, sealing by fusing are in ampoule bottle, and 121 DEG C × 15min sterilizing, to obtain final product.
Embodiment 3
Preparation technology
Take the adjuvant sodium pyrosulfite of recipe quantity, propylene glycol, sodium citrate, citric acid to be successively dissolved in recipe quantity water for injection, add recipe quantity phloroglucinol dihydrate and dissolve; Add 0.1%(mass volume ratio) powdery pharmaceutical active carbon, stirring and adsorbing 15min; First use 0.45 μm of filtering with microporous membrane decarburization, then use 0.22 μm of microporous filter membrane aseptic filtration; Get portion filtrate and carry out intermediates content inspection; Fill, sealing by fusing are in ampoule bottle, and 121 DEG C × 15min sterilizing, to obtain final product.
Embodiment 4
Taking the adjuvant sodium pyrosulfite of recipe quantity, propylene glycol, sodium citrate, citric acid is successively dissolved in recipe quantity water for injection, adds recipe quantity phloroglucinol dihydrate under nitrogen protection and dissolves; Add 0.1%(mass volume ratio) powdery pharmaceutical active carbon, under nitrogen protection stirring and adsorbing 15min; First use 0.45 μm of filtering with microporous membrane decarburization, then use 0.22 μm of microporous filter membrane aseptic filtration; Get portion filtrate and carry out intermediates content inspection, all the other filtrates pass into nitrogen protection; Inflated with nitrogen fill, sealing by fusing are in ampoule bottle, and 121 DEG C × 15min sterilizing, to obtain final product.
Embodiment 5 frozen process experiment
Frozen process experiment is carried out with reference to example 1, reference example 2, reference example 3, reference example 4, embodiment 1, embodiment 2, embodiment 3, embodiment 4 gained sample, investigate the change of its related substance, content, pH and color, assay method is with reference to " national drug standards: phloroglucinol injection YBH22452004 ", and colour measurement is according to Chinese Pharmacopoeia 2010 editions standard color solutions.As shown in Table 2, the result of table one measured by first 0 day of freeze thawing, carry out related substance detection to reference example and embodiment phloroglucinol raw material used, result is 0.12% to result simultaneously.The result of table two for recording after freeze thawing.
Table one 0 day measurement result
Table two frozen process experiment result
Embodiment 624 months is long-term
Carry out that temperature is 25 DEG C with reference to example 1, reference example 2, reference example 3, reference example 4, embodiment 1, embodiment 2, embodiment 3, embodiment 4 gained sample according to method described in Chinese Pharmacopoeia, humidity is long-time stability experiments in 24 months under 75% condition.
(1) investigate the change of its related substance, content, pH and color, assay method is with reference to " national drug standards: phloroglucinol injection YBH22452004 ", and colour measurement is according to Chinese Pharmacopoeia 2010 editions standard color solutions.
Result as shown in Table 3.
Table three 24 months 40 DEG C of high temperature experimental results
(2) visible foreign matters checking experiment
Instrument: YB-2 type clarity test instrument
Method: respectively get 20 sample determinations, assay method is with reference to " Chinese Pharmacopoeia version in 2010 two general rules (annex Ⅸ H) ", and experimental result as shown in Table 4.
Table four visible foreign matters checking experiment result
Claims (10)
1. a phloroglucinol injection, be made up of active component phloroglucinol, antioxidant sodium pyrosulfite, propylene glycol, the pH adjusting agent being selected from citric acid and sodium citrate and water for injection, wherein the weight ratio of phloroglucinol, antioxidant sodium pyrosulfite, propylene glycol, citric acid, sodium citrate, water for injection is: 40:0.05 ~ 0.20:200 ~ 250:6 ~ 10:5 ~ 8:3750 ~ 3800.
2. phloroglucinol injection according to claim 1, its active component is phloroglucinol anhydride or phloroglucinol dihydrate.
3. phloroglucinol injection according to claim 1, is characterized in that the weight ratio of phloroglucinol, sodium pyrosulfite, propylene glycol, citric acid, sodium citrate, water for injection is: 40:0.05:200:6:8:3800.
4. phloroglucinol injection according to claim 1, is characterized in that the weight ratio of phloroglucinol, sodium pyrosulfite, propylene glycol, citric acid, sodium citrate, water for injection is: 40:0.20:225:10:5:3775.
5. phloroglucinol injection according to claim 1, is characterized in that the weight ratio of phloroglucinol, sodium pyrosulfite, propylene glycol, citric acid, sodium citrate, water for injection is: 40:0.1:250:8:6.5:3750.
6. the preparation method of phloroglucinol injection according to claim 1, it is characterized in that it is prepared by the following method: take the antioxidant sodium pyrosulfite of recipe quantity, propylene glycol and pH adjusting agent and be dissolved in recipe quantity water for injection, add recipe quantity phloroglucinol and dissolve; Add active carbon, stirring and adsorbing; Fill after filtering, sealing by fusing are in ampoule bottle, and sterilizing, to obtain final product.
7. the preparation method of phloroglucinol injection according to claim 1, it is characterized in that it is prepared by the following method: take the antioxidant sodium pyrosulfite of recipe quantity, propylene glycol and pH adjusting agent and be dissolved in recipe quantity water for injection, add recipe quantity phloroglucinol under nitrogen protection and dissolve; Add active carbon, under nitrogen protection stirring and adsorbing; Inflated with nitrogen fill after filtering, sealing by fusing are in ampoule bottle, and sterilizing, to obtain final product.
8. the preparation method of the phloroglucinol injection described in claim 6-7, it is characterized in that described active carbon is powdery pharmaceutical charcoal, its consumption is 0.01% ~ 0.1%, preferably 0.1%; The stirring and adsorbing time is 10 ~ 20min, preferred 15min.
9. the preparation method of the phloroglucinol injection described in claim 6-7, it is characterized in that described filtration comprises the microporous filter membrane or titanium filter stick or polysulfone filter filtration decarburization first selecting 0.45 ~ 1 μm, then select microporous filter membrane or the polysulfone filter aseptic filtration of 0.22 μm.
10. the preparation method of the phloroglucinol injection described in claim 6-7, it is characterized in that described sterilizing methods is final sterilization method, sterilising conditions is 121 DEG C of moist heat sterilization 8 ~ 30min, preferably 121 DEG C of moist heat sterilization 10 ~ 20min, further preferred 121 DEG C of moist heat sterilization 15min.
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| CN201310308262.XA CN104323986A (en) | 2013-07-22 | 2013-07-22 | Phloroglucinol injection and preparation method thereof |
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Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106539753A (en) * | 2016-11-01 | 2017-03-29 | 南京生命能科技开发有限公司 | A kind of phloroglucinol injection and preparation method thereof |
| CN106963779A (en) * | 2017-04-20 | 2017-07-21 | 南京正科医药股份有限公司 | A kind of production method of compound potassium dihydrogn phosphate |
| CN107233306A (en) * | 2017-07-03 | 2017-10-10 | 华润双鹤利民药业（济南）有限公司 | A kind of caffeine citrate parenteral solution and preparation method thereof |
| CN108341742A (en) * | 2017-01-23 | 2018-07-31 | 上海鼎雅药物化学科技有限公司 | The salt of phloroglucin and its application in the treatment |
| CN108498492A (en) * | 2018-02-23 | 2018-09-07 | 广东医科大学 | A kind of purposes of phloroglucin in preparing the drug for promoting union |
| CN110652600A (en) * | 2019-09-27 | 2020-01-07 | 浙江都邦药业股份有限公司 | Multistage sterilization and disinfection equipment for injection and disinfection process thereof |
| CN111252278A (en) * | 2020-01-17 | 2020-06-09 | 上海华源安徽锦辉制药有限公司 | Production process of plastic bottle infusion solution |
| CN115721631A (en) * | 2022-12-08 | 2023-03-03 | 绪必迪药业(沧州)有限公司 | Preparation method of phloroglucinol injection |
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2013
- 2013-07-22 CN CN201310308262.XA patent/CN104323986A/en active Pending
Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106539753A (en) * | 2016-11-01 | 2017-03-29 | 南京生命能科技开发有限公司 | A kind of phloroglucinol injection and preparation method thereof |
| CN108341742A (en) * | 2017-01-23 | 2018-07-31 | 上海鼎雅药物化学科技有限公司 | The salt of phloroglucin and its application in the treatment |
| CN106963779A (en) * | 2017-04-20 | 2017-07-21 | 南京正科医药股份有限公司 | A kind of production method of compound potassium dihydrogn phosphate |
| CN107233306A (en) * | 2017-07-03 | 2017-10-10 | 华润双鹤利民药业（济南）有限公司 | A kind of caffeine citrate parenteral solution and preparation method thereof |
| CN108498492A (en) * | 2018-02-23 | 2018-09-07 | 广东医科大学 | A kind of purposes of phloroglucin in preparing the drug for promoting union |
| CN110652600A (en) * | 2019-09-27 | 2020-01-07 | 浙江都邦药业股份有限公司 | Multistage sterilization and disinfection equipment for injection and disinfection process thereof |
| CN111252278A (en) * | 2020-01-17 | 2020-06-09 | 上海华源安徽锦辉制药有限公司 | Production process of plastic bottle infusion solution |
| CN115721631A (en) * | 2022-12-08 | 2023-03-03 | 绪必迪药业(沧州)有限公司 | Preparation method of phloroglucinol injection |
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Application publication date: 20150204 |